Therapeutic drug monitoring of doxorubicin in paediatric oncology using capillary electrophoresis

A method for the determination of doxorubicin and its main metabolite doxor ubicinol in human plasma is described. Two different sample preparation pro cedures are applied depending on the expected concentration: To monitor the peak plasma levels, 10 mu L of plasma are deproteinated with acetonitrile. After centrifugation, the supernatant is directly applied to the capillary by hydrodynamic injection. For the determination of lower amounts of doxor ubicin and its main metabolite doxorubicinol 100 mu L of plasma is extracte d by liquid-/liquid extraction with chloroform. After evaporation of the or ganic phase, the sample is reconstituted in acetonitrile/water (95/5 v/v) a nd injected into the capillary by electrokinetic injection. Idarubicin serv es as the internal standard. Laser-induced fluorescence detection with an A r-ion laser emitting at 488 nm and a 520 nm cut-off filter is used for dete ction. The accuracy of the method was calculated to be 3.0% at higher conce ntrations and 15.0% at the limit of quantification. Reproducibility data ar e in accordance to the generally accepted criteria for bioanalytical method s. The limit of quantification is 2 mu g/L, enabling us to monitor doxorubi cin plasma levels for several days after application. Noninvasive blood sam pling (from the fingertip) using heparinized capillaries was, found to be a simple and convenient procedure and provides reproducible data. Initial re sults show high interindividual variability in doxorubicin peak plasma leve ls.